Molecular screening of the TGIF gene in holoprosencephaly: identification of two novel mutations

• Published in: Human genetics Vol. 112; no. 2; pp. 131 - 134
• Main Authors: AGUILELLA, Céline, DUBOURG, Christèle, ATTIA-SOBOL, Jocelyne, VIGNERON, Jacqueline, BLAYAU, Martine, PASQUIER, Laurent, LAZARO, Leila, ODENT, Sylvie, DAVID, Véronique
• Format: Journal Article
• Language: English
• Published: Heidelberg Springer 01.02.2003; Berlin Springer Nature B.V; New York, NY
• Subjects: Adult; Biological and medical sciences; Cells, Cultured; Codon, Nonsense - genetics; DNA - genetics; DNA - metabolism; DNA Mutational Analysis; Female; Fetus - pathology; Fundamental and applied biological sciences. Psychology; Genes, Homeobox - genetics; Genes. Genome; Holoprosencephaly - genetics; Homeodomain Proteins - genetics; Humans; Infant; Male; Malformations of the nervous system; Medical sciences; Molecular and cellular biology; Molecular genetics; Mutation, Missense - genetics; Neurology; Repressor Proteins - genetics; Human; Arhinencephaly; Screening; Nervous system diseases; Malformation; Central nervous system disease; Identification; Mutation; Congenital disease; Cerebral disorder
• ISSN: 0340-6717; 1432-1203
• DOI: 10.1007/s00439-002-0862-8

Holoprosencephaly (HPE) is the most common severe brain anomaly in humans, which results from incomplete cleavage of the forebrain during early embryogenesis. The aetiology of HPE is very heterogeneous. Among the genetic factors, TGIF ( TG-interacting factor), which codes for a transcription factor modulating the signalling pathway of TGF-beta, was previously implicated. We investigated 127 HPE probands by sequencing their TGIF gene and identified the first nonsense mutation reported so far and also a novel missense mutation, in two families that presented a large range of disease severity. The low number of mutations in TGIF suggests that this gene has no major contribution to the aetiology of HPE and our study confirms the wide clinical heterogeneity of the disease.